Peripheral neuropathy is one of the commonest and most debilitating complications of diabetes mellitus. However, very little is known about the pathogenetic mechanisms of this disorder. It is our long range goal to elucidate such mechanisms at the molecular level, and to find therapeutic ways of altering these that could be clinically useful. A major problem in this area of research has been the lack of an animal model which spontaneously reproduces the human disorder. The BB Wistar rat is a relatively new and very promising animal model of diabetes which spontaneously develops several abnormalities in its peripheral nervous system. Our preliminary data show that there are abnormalities in the lipid compositions of nervous tissues of these animals which indicate that there may be a metabolic disorder of the Schwann cell-myelin unit. It is the purpose of the experiments in this proposal to determine more precisely the biochemical nature and extent of this disorder. Towards that end, four aspects of nerve biochemistry of the BB Wistar diabetic rat will be studied: (a) Compositional changes in several important constituents during growth and maturation of peripheral nerve. (b) Protein and lipid compositions of peripheral nerve myelin. (c) Compositional changes during Wallerian degeneration of peripheral nervous systems. The results of these neurochemical studies not only will help to clrify the nature and extent of this disorder in the BBW rat, but should yield insights into the pathogenesis of human diabetic neuropathy.